Cytogenetics and Granulopoietic Effects of Bone Marrow Fibroblastic Cells in Fanconi's Anaemia

S ummary. To determine if abnormalities exist in the bone marrow stroma in Fanconi's anaemia, we studied the cytogenetic composition of in vitro bone marrow fibroblastic cells (FC) from a patient with this disorder and compared it to those obtained from skin fibroblasts, peripheral blood lymphocytes, and direct bone marrow preparations. The presence of granulocytic progenitors in bone marrow and T lymphocyte colonies in peripheral blood was also determined in addition to the ability of this patient's FC to stimulate normal granulocytic progenitors. We found that the FC had far fewer chromosomal abnormalities and stimulated normally the growth of granulocyte colonies. Granulocyte progenitors were not found, but T lymphocyte colonies were abundant. These results support the concept that a defect in haematopoietic stromal elements is not responsible for the aplasia developing in the disorder.     

Inversion of chromosome 12 and lineage promiscuity in hematologic malignancies

Rearrangements of the short arm of chromosome 12 are among the most common aberrations found in hematologic malignancies, including myelodysplastic syndromes, acute myelocytic leukemias, acute lymphoblastic leukemias, and non-Hodgkin lymphomas. We report on a group of 46 patients with a variety of myelocytic and lymphoid malignancies, all with an inversion of chromosome 12. Both pericentric and paracentric inversions occurred. The identified hotspots for breakage were p13 and q24. These correspond to gene-rich areas of known chromosome instability. The inv(12) is difficult to detect and may be misinterpreted as a partial deletion by routine cytogenetics. Fluorescence in situ hybridization studies revised the G-banding interpretations of a deleted 12p in some cases to an inversion. The inv(12) may occur as the sole abnormality in both myelocytic and lymphoid malignancies, suggesting lineage promiscuity as seen with MLL and ETV6 gene disruptions. The majority of patients with the inv(12) had complex karyotypic changes that predicted a poor prognosis. Of the 24 patients with known clinical follow-up, many were refractory to chemotherapy and overall survival was short.